Preclinical study: antibiotics affect a man

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In a new study, Cedars-Sinai researchers have found that antibiotics have sex-specific effects on the gut microbiome composition of male and female lab rats. The results, published in the journal Frontiers in microbiologycould have implications for the use of drugs in humans to treat or prevent bacterial infection.

“We found that administration of a multidrug antibiotic cocktail to rats resulted in significant, gender-specific changes in both the feces, or large intestine, and the small intestine. For example, greater loss diversity of microbes in the feces and small intestine was observed in male rodents than in females,” said Ruchi Mathur, MDprincipal investigator of the study.

“Changes in the diversity of the gut microbiome could have a negative impact. Previous gut health studies have demonstrated that overall microbial diversity promotes vitality and resilience, which often contributes to a healthier gut,” said endocrinologist Mathur.

In the controlled study, Cedars-Sinai investigators Medically Associated Science and Technology (MAST) Program compared the gut microbe composition of male and female rats before, during, and after treatment with broad-spectrum antibiotics, including vancomycin, ampicillin, metronidazole, and neomycin.

“We followed the rats for a period after stopping the antibiotics and found that many of the sex-specific changes we observed during treatment persisted. The constellation of microbes in the gut did not revert to their original pre-antibiotic compositions in either gender over the duration of the study,” said research associate Gonzalo Parodi, first author of the article.

Some studies have identified sex-specific effects of antibiotics on the large intestine (feces) microbiome in mice. But the Cedars-Sinai researchers point out that this is the first study to also look at antibiotic-induced changes in the small intestine microbiome and to also use male and female rats which showed no significant differences. in the composition of the microbiome before treatment.

“It is difficult to disentangle the impact of drugs if the gut microbiomes of laboratory animals are different to begin with. We used rats with similar gut profiles from the start. This allowed us to identify changes in the microbiomes of male and female rats that could be attributed specifically to the impact of antibiotics during and after drug exposure,” said Mark Pimentel, MDdirector of the MAST program and co-author of the study.

Further studies are needed using different combinations of antibiotics and exposure times. The researchers say that if these findings hold true for humans, the research could have implications for how antibiotics are prescribed.

“Sex is a biological variable, and like any variable, it must be taken into consideration in fundamental and medical research. Currently, we consider factors such as kidney function and weight when administering medication to patients. According to the results of further research, particularly in humans, the gender of patients may one day be an important consideration when prescribing antibiotics,” said Mathur.


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